Smoking cessation

Smoking cessation (colloquially quitting smoking) is the process of discontinuing tobacco smoking. Tobacco contains nicotine, which is addictive,[1] making the process of quitting often very prolonged and difficult.

Smoking cessation can be achieved with or without assistance from healthcare professionals, or the use of medications. However, a combination of personal efforts and medications proves more effective to many smokers.[2] Methods that have been found to be effective include interventions directed at or via health care providers and health care systems; medications including nicotine replacement therapy (NRT) and varenicline; individual and group counselling. Although stopping smoking can cause short-term side effects such as reversible weight gain, smoking cessation services and activities are cost-effective because of the positive health benefits.

In a growing number of countries, there are more ex-smokers than smokers.[2]

Early "failure" is a normal part of trying to stop, and more than one attempt at stopping smoking prior to longer-term success is common.[2]

NRT, other prescribed pharmaceuticals, and professional counselling or support also help many smokers.[2]

However, up to three-quarters of ex-smokers report having quit without assistance ("cold turkey" or cut down then quit), and cessation without professional support or medication may be the most common method used by ex-smokers.[2]

Major reviews of the scientific literature on smoking cessation include:

Systematic reviews of the Cochrane Tobacco Addiction Group of the Cochrane Collaboration.[5] As of 2012, this independent, international, not-for-profit organization has published over 60 systematic reviews "on interventions to prevent and treat tobacco addiction"[5] which will be referred to as "Cochrane reviews."

Clinical Practice Guideline: Treating Tobacco Use and Dependence: 2008 Update of the United States Department of Health and Human Services, which will be referred to as the "2008 Guideline."[6] The Guideline was originally published in 1996[7] and revised in 2000.[8] For the 2008 Guideline, experts screened over 8700 research articles published between 1975 and 2007.[6]:13–14 More than 300 studies were used in meta-analyses of relevant treatments; an additional 600 reports were not included in meta-analyses, but helped formulate the recommendations.[6]:22 Limitations of the 2008 Guideline include its not evaluating studies of "cold turkey" methods ("unaided quit attempts") and its focus on studies that followed up subjects only to about 6 months after the "quit date" (even though almost one-third of former smokers who relapse before one year will do so 7–12 months after the "quit date").[6]:19,23[9][10]

As it is common for ex-smokers to have made a number of attempts (often using different approaches on each occasion) to stop smoking before achieving long-term abstinence, identifying which approach or technique is eventually most successful is difficult; it has been estimated, for example, that "only about 4% to 7% of people are able to quit smoking on any given attempt without medicines or other help.".[11] However, in analysing a 1986 U.S. survey, Fiore et al. (1990) found that 95% of former smokers who had been abstinent for 1–10 years had made an unassisted last quit attempt.[12] The most frequent unassisted methods were "cold turkey" and "gradually decreased number" of cigarettes.[12] A 1995 meta-analysis estimated that the quit rate from unaided methods was 7.3% after an average of 10 months of follow-up.[13]

"Cold turkey" is a colloquial term indicating abrupt withdrawal from an addictive drug, and in this context indicates sudden and complete cessation of all nicotine use. In three studies, it was the quitting method cited by 76%,[14] 85%,[12] or 88%[15] of long-term successful quitters. In a large British study of ex-smokers in the 1980s, before the advent of pharmacotherapy, 53% of the ex-smokers said that it was "not at all difficult" to stop, 27% said it was "fairly difficult", and the remaining 20% found it very difficult.[2]

The American Cancer Society estimates that "between about 25% and 33% of smokers who use medicines can stay smoke-free for over 6 months."[11] Single medications include:

Nicotine replacement therapy (NRT): Five medications approved by the U.S. Food and Drug Administration (FDA) deliver nicotine in a form that does not involve the risks of smoking. NRTs are meant to be used for a short period of time and should be tapered down to a low dose before stopping. The five NRT medications, which in a Cochrane review increased the chances of stopping smoking by 50 to 70% compared to placebo or to no treatment,[16] are: transdermal nicotine patches, gum, lozenges,sprays, inhalers.

A Cochrane review found further increased chance of success in a combination of the nicotine patch and a faster acting form.[16] A study found that 93 percent of over-the-counter NRT users relapse and return to smoking within six months.[17]

Antidepressant: The antidepressants bupropion and nortriptyline help in long-term smoking cessation and adverse events with both drugs are rarely serious enough to cause stopping of the medication. The evidence also points out that bupropion is less effective than varenicline however this needs to be further validated.[18] Bupropion is contraindicated in epilepsy, seizure disorder; anorexia/bulimia (eating disorders), in those who have use the antidepressant drugs MAO inhibitors within 14 days, patients undergoing abrupt discontinuation of ethanol or sedatives (including benzodiazepines such as Valium).[19][20]Moclobemide does not result in long term benefit.[18]

Varenicline decreases the urge to smoke and reduces withdrawal symptoms.[21] A systematic reviews has found varenicline more effective than bupropion.[18] A table in the 2008 Guideline indicates that 2 mg/day of varenicline leads to the highest abstinence rate (33.2%) of any single therapy, while 1 mg/day leads to an abstinence rate of 25.4%.[6]:109 A 2011 Cochrane review of 15 studies (13 of which had been sponsored by Pfizer) found that varenicline was significantly superior to bupropion at one year but that varenicline and nicotine patches produced the same level of abstinence at 24 weeks.[22] A 2011 review of double-blind studies found that varenicline has increased risk of serious adverse cardiovascular events compared with placebo.[23] Varenicline may cause neuropsychiatric side effects; for example, in 2008 the UK. Medicines and Healthcare products Regulatory Agency issued a warning about possible suicidal thoughts and suicidal behavior associated with varenicline.[24]

Clonidine may reduce withdrawal symptoms and "approximately doubles abstinence rates when compared to a placebo," but its side effects include dry mouth and sedation, and abruptly stopping the drug can cause high blood pressure and other side effects.[6]:55,116–117[25]

The 2008 US Guideline specifies that three combinations of medications are effective:[6]:118–120

Long-term nicotine patch and ad libitum NRT gum or spray

Nicotine patch and nicotine inhaler

Nicotine patch and bupropion (the only combination that the US FDA has approved for smoking cessation)

Gradual reduction involves slowly reducing one's daily intake of nicotine. This can theoretically be accomplished through repeated changes to cigarettes with lower levels of nicotine, by gradually reducing the number of cigarettes smoked each day, or by smoking only a fraction of a cigarette on each occasion. A 2009 systematic review by researchers at the University of Birmingham found that gradual nicotine replacement therapy could be effective in smoking cessation.[26][27] A 2010 Cochrane review found that abrupt cessation and gradual reduction with pre-quit NRT produced similar quit rates whether or not pharmacotherapy or psychological support was used. [28][29] According to a more recent 2012 Cochranesystematic review analysis of 10 studies and 3670 patients, overall relative risk reduction between smokers who attempted to quit with abrupt cessation or with gradual reduction techniques was 0.06. This analysis demonstrated that there was no significant difference in quit rates between smokers who quit by gradual reduction or abrupt cessation as measured by abstinence from smoking of at least six months from the quit day, suggesting that patients who want to quit can choose between these two methods.[30]

A Cochrane review found evidence that community interventions using "multiple channels to provide reinforcement, support and norms for not smoking" had an effect on smoking cessation outcomes among adults.[31] Specific methods used in the community to encourage smoking cessation among adults include:

Policies making workplaces[14] and public places smoke-free. It is estimated that "comprehensive clean indoor laws" can increase smoking cessation rates by 12%–38%.[32] In 2008, the New York State of Alcoholism and Substantance Abuse Services banned smoking by patients, staff and volunteers at 1,300 addiction treatment centers.[33]

Voluntary rules making homes smoke-free, which are thought to promote smoking cessation.[14][34]

Increasing the price of tobacco products, for example by taxation. The US Task Force on Community Preventive Services found "strong scientific evidence" that this is effective in increasing tobacco use cessation.[35]:28–30 It is estimated that an increase in price of 10% will increase smoking cessation rates by 3–5%.[32]

Mass media campaigns. The US Task Force on Community Preventive Services declared that "strong scientific evidence" existed for these when "combined with other interventions",[35]:30–32 but a Cochrane review concluded that it was "difficult to establish their independent role and value".[36]

Smoking-cessation support is often offered over the internet, over the telephone quitlines[37][38] (e.g., the US toll-free number 1-800-QUIT-NOW), or in person. Three meta-analyses have concluded that telephone cessation support is effective when compared with minimal or no counselling or self-help, and that telephone cessation support with medication is more effective than medication alone.[6]:91–92[35]:40–42[39]

The Freedom From Smoking group clinic includes eight sessions and features a step-by-step plan for quitting smoking. Each session is designed to help smokers gain control over their behavior. The clinic format encourages participants to work on the process and problems of quitting both individually and as part of a group[47]

Multiple formats of psychosocial interventions increase quit rates: 10.8% for no intervention, 15.1% for one format, 18.5% for 2 formats, and 23.2% for three or four formats.[6]:91

The Transtheoretical Model including "stages of change" has been used in tailoring smoking cessation methods to individuals.[48][49][50][51] However, a 2010 Cochrane review concluded that "stage-based self-help interventions (expert systems and/or tailored materials) and individual counselling were neither more nor less effective than their non-stage-based equivalents."[52]

Some health organizations manage text messaging services to help people avoid smoking

A 2005 Cochrane review found that self-help materials may produce only a small increase in quit rates.[53] In the 2008 Guideline, "the effect of self-help was weak," and the number of types of self-help did not produce higher abstinence rates.[6]:89–91 Nevertheless, self-help modalities for smoking cessation include:

Interactive web-based and stand-alone computer programs and online communities which assist participants in quitting, such as EX and QuitNet. For example, "quit meters" keep track of statistics such as how long a person has remained abstinent.[59] In the 2008 US Guideline, there was no meta-analysis of computerised interventions, but they were described as "highly promising."[6]:93–94 A meta-analysis published in 2009,[60] a Cochrane review published in 2010,[61] and a 2011 systematic review[62] found the evidence base for such interventions weak.

Mobile phone-based interventions: A 2009 Cochrane review stated that "more evidence is needed" to determine the effectiveness of such interventions.[63] As of 2009, a randomised trial of mobile phone-based smoking cessation support was underway in the UK.[64]

Spirituality: In one survey of adult smokers, 88% reported a history of spiritual practice or belief, and of those more than three-quarters were of the opinion that using spiritual resources may help them quit smoking.[68]

Various methods exist which allow a smoker to see the impact of their tobacco use, and the immediate effects of quitting. Using biochemical feedback methods can allow tobacco-users to be identified and assessed, and the use of monitoring throughout an effort to quit can increase motivation to quit.[69][70]

Breath carbon monoxide (CO) monitoring: Because carbon monoxide is a significant component of cigarette smoke, a breath carbon monoxide monitor can be used to detect recent cigarette use. Carbon monoxide concentration in breath has been shown to be directly correlated with the CO concentration in blood, known as percent carboxyhemoglobin. The value of demonstrating blood CO concentration to a smoker through a non-invasive breath sample is that it links the smoking habit with the physiological harm associated with smoking.[71] Within hours of quitting, CO concentrations show a noticeable decrease, and this can be encouraging for someone working to quit. Breath CO monitoring has been utilized in smoking cessation as a tool to provide patients with biomarker feedback, similar to the way in which other diagnostic tools such as the stethoscope, the blood pressure cuff, and the cholesterol test have been used by treatment professionals in medicine.[69]

Cotinine: A metabolite of nicotine, cotinine is present in smokers. Like carbon monoxide, a cotinine test can serve as a reliable biomarker to determine smoking status.[72] Cotinine levels can be tested through urine, saliva, blood, or hair samples, with one of the main concerns of cotinine testing being the invasiveness of typical sampling methods.

While both measures offer high sensitivity and specificity, they differ in usage method and cost. As an example, breath CO monitoring is non-invasive, while cotinine testing relies on a bodily fluid. These two methods can be used either alone or together, for example, in a situation where abstinence verification needs additional confirmation.[73]

One 2008 Cochrane review concluded that "incentives and competitions have not been shown to enhance long-term cessation rates."[74] A different 2008 Cochrane review found that one type of competition, "Quit and Win," did increase quit rates among participants.[75]

Interventions delivered via healthcare providers and healthcare systems have been shown to improve smoking cessation among people who visit those providers.

A clinic screening system (e.g., computer prompts) to identify whether or not a person smokes doubled abstinence rates, from 3.1% to 6.4%.[6]:78–79 Similarly, the Task Force on Community Preventive Services determined that provider reminders alone or with provider education are effective in promoting smoking cessation.[35]:33–38

A 2008 Guideline meta-analysis estimated that physician advice to quit smoking led to a quit rate of 10.2%, as opposed to a quit rate of 7.9% among patients who did not receive physician advice to quit smoking.[6]:82–83 A Cochrane review found that even brief advice from physicians had "a small effect on cessation rates."[76] However, one study from Ireland involving vignettes found that physicians' probability of giving smoking cessation advice declines with the patient's age,[77] and another study from the U.S. found that only 81% of smokers age 50 or greater received advice on quitting from their physicians in the preceding year.[78]

For one-to-one or person-to-person counselling sessions, the duration of each session, the total amount of contact time, and the number of sessions all correlated with the effectiveness of smoking cessation. For example, "Higher intensity" interventions (>10 minutes) produced a quit rate of 22.1% as opposed to 10.9% for "no contact"; over 300 minutes of contact time produced a quit rate of 25.5% as opposed to 11.0% for "no minutes"; and more than 8 sessions produced a quit rate of 24.7% as opposed to 12.4% for 0–1 sessions.[6]:83–86

Both physicians and non-physicians increased abstinence rates compared with self-help or no clinicians.[6]:87–88 For example, a Cochrane review of 31 studies found that nursing interventions increased the likelihood of quitting by 28%.[79]

Dental professionals also provide a key component in increasing tobacco abstinence rates in the community through counseling patients on the effects of tobacco on oral health in conjunction with an oral exam.[80]

According to the 2008 Guideline, based on two studies the training of clinicians in smoking cessation methods may increase abstinence rates;[6]:130 however, a Cochrane review found and measured that such training decreased smoking in patients.[81]

Reducing or eliminating the costs of cessation therapies for smokers increased quit rates in three meta-analyses.[6]:139–140[35]:38–40[82]

In one systematic review and meta-analysis, multi-component interventions increased quit rates in primary care settings.[83] "Multi-component" interventions were defined as those that combined two or more of the following strategies known as the "5 A's":[6]:38–43

Electronic cigarette: In 2014 The Royal College of Physicians in London published an article advocating the use of electronic cigarettes as a smoking cessation tool.[84] In September 2008, the World Health Organization stated that it does not consider the electronic cigarette to be a legitimate smoking cessation aid because "no rigorous, peer-reviewed studies have been conducted showing that the electronic cigarette is a safe and effective nicotine replacement therapy."[85] A more recent research study, “Electronic cigarettes for smoking cessation: a randomized controlled trial", funded by the Health Research Council of New Zealand, was far less convinced that e-cigarettes were not as viable an option as traditional modalities. The study was conducted between Sept 6,2011 and July 5, 2013 with a sample size of 657. Their interpretation of the results:
"E-cigarettes, with or without nicotine-based ejuices, were modestly effective at helping smokers to quit, with similar achievement of abstinence as with nicotine patches, and few adverse events. Uncertainty exists about the place of e-cigarettes in tobacco control, and more research is urgently needed to clearly establish their overall benefits and harms at both individual and population levels".[86]

Chewing cinnamon sticks or gum has been recommended when trying to quit the use of tobacco.[87]

Acupuncture: Acupuncture has been explored as an adjunct treatment method for smoking cessation.[88] A Cochrane review concluded that acupuncture "do[es] not appear to help smokers who are trying to quit",[89] a meta-analysis from the 2008 Guideline showed no difference between acupuncture and placebo,[6]:99–100 and the 2008 Guideline found no scientific studies supporting laser therapy based on acupuncture principles but without the needles.[6]:99

Aromatherapy: A 2006 book reviewing the scientific literature on aromatherapy[90] identified only one study on smoking cessation and aromatherapy; the study found that "inhalation of vapor from black pepper extract reduces smoking withdrawal symptoms".[91]

Hypnosis: Hypnosis often involves the hypnotherapist suggesting to the patient the unpleasant outcomes of smoking.[92] Clinical trials studying hypnosis and hypnotherapy as a method for smoking cessation have been inconclusive;[6]:100[93][94][95] however, a randomized trial published in 2008 found that hypnosis and nicotine patches "compares favorably" with standard behavioral counseling and nicotine patches in 12-month quit rates.[96]

Herbs: Many herbs have been studied as a method for smoking cessation, including lobelia and St John's wort.[97][98] The results are inconclusive, but St. Johns Wort shows few adverse events. Lobelia has been used to treat respiratory diseases like asthma and bronchitis, and has been used for smoking cessation because of chemical similarities to tobacco; lobelia is now listed in the FDA's Poisonous Plant Database.[99][100] Lobelia can still be found in many products sold for smoking cessation and should be used with caution.

Smokeless tobacco: There is little smoking in Sweden, which is reflected in the very low cancer rates for Swedish men. Use of snus (a form of steam-pasteurised, rather than heat-pasteurised, air-cured smokeless tobacco) is an observed cessation method for Swedish men and even recommended by some Swedish doctors.[101]

There are many other measures used in an effort to quit smoking which lack evidence including: a substance put on the cigarette called NicoBloc.[102] Due to the lack of evidence they are typically not recommended.[103]

A Cochrane review, mainly of studies combining motivational enhancement and psychological support, concluded that "complex approaches" for smoking cessation among young people show promise.[104] The 2008 US Guideline recommends counselling-style support for adolescent smokers on the basis of a meta-analysis of seven studies.[6]:159–161 Neither the Cochrane review nor the 2008 Guideline recommends medications for adolescents who smoke.

Smoking during pregnancy can cause adverse health effects in both the woman and the fetus. The 2008 US Guideline determined that "person-to-person psychosocial interventions" (typically including "intensive counseling") increased abstinence rates in pregnant women who smoke to 13.3%, compared with 7.6% in usual care.[6]:165–167 Mothers who smoke during pregnancy have a greater tendency towards premature births. Their babies are often underdeveloped, have smaller organs, and weigh much less compared with the normal baby. In addition, these babies have worse immune systems, making them more susceptible to many diseases in early childhood, such as middle ear inflammations and asthmatic bronchitis which can bring about a lot of agony and suffering. As well, there is a high chance that they will become smokers themselves when grown up.

It is a widely spread myth that a female smoker can cause harm to her fetus by quitting immediately upon discovering that she is with child. Though this idea does seem to follow logic, it is not based on any medical study or fact.[106]

Percent increase of success for six months over unaided attempts for each type of quitting (chart from West & Shiffman based on Cochrane review data[109]:59

Smokers who are hospitalised may be particularly motivated to quit.[6]:149–150 A 2007 Cochrane review found that interventions beginning during a hospital stay and continuing for one month or more after discharge were effective in producing abstinence.[110]

Comparison of success rates across interventions can be difficult because of different definitions of "success" across studies.[11] Robert West and Saul Shiffman, authorities in this field recognised by government health departments in a number of countries,[109]:73,76,80 have concluded that, used together, "behavioural support" and "medication" can quadruple the chances that a quit attempt will be successful.

A 2008 systematic review in the European Journal of Cancer Prevention found that group behavioural therapy was the most effective intervention strategy for smoking cessation, followed by bupropion, intensive physician advice, nicotine replacement therapy, individual counselling, telephone counselling, nursing interventions, and tailored self-help interventions; the study did not discuss varenicline.[32]

Individuals who sustained damage to the insula were able to more easily abstain from smoking.[111]

Quitting can be harder for individuals with dark pigmented skin compared to individuals with pale skin since nicotine has an affinity for melanin-containing tissues. Studies suggest this can cause the phenomenon of increased nicotine dependence and lower smoking cessation rate in darker pigmented individuals.[112]

There is an important social component to smoking. A 2008 study of a densely interconnected network of over 12,000 individuals found that smoking cessation by any given individual reduced the chances of others around them lighting up by the following amounts: a spouse by 67%, a sibling by 25%, a friend by 36%, and a coworker by 34%.[113] Nevertheless, a Cochrane review determined that interventions to increase social support for a smoker's cessation attempt did not increase long-term quit rates.[114]

Smokers who are trying to quit are faced with social influences that may persuade them to conform and continue smoking. Cravings are easier to detain when one's environment does not provoke the habit. If a person who stopped smoking has close relationships with active smokers they are often put into situations that make the urge to conform more tempting. However, in a small group with at least one other not smoking, the likelihood of conformity decreases. The social influence to smoke cigarettes has been proven to rely on simple variables. One researched variable depends on whether the influence is from a friend or non-friend.[115] the research shows that individuals are 77% more likely to conform to non-friends, while close friendships decrease conformity. Therefore, if an acquaintance offers a cigarette as a polite gesture, the person who has stopped smoking will be more likely to break his commitment than if a friend had offered.

Relapse (resuming smoking after quitting) has been related to psychological issues such as low self-efficacy[117] or non-optimal coping responses;[118] however, psychological approaches to prevent relapse have not been proven to be successful.[119] In contrast, varenicline may help some relapsed smokers.[119]

In a 2007 review of the effects of abstinence from tobacco, Hughes concluded that "anger, anxiety, depression, difficulty concentrating, impatience, insomnia, and restlessness are valid withdrawal symptoms that peak within the first week and last 2–4 weeks."[20] In contrast, "constipation, cough, dizziness, increased dreaming, and mouth ulcers" may or may not be symptoms of withdrawal, while drowsiness, fatigue, and certain physical symptoms ("dry mouth, flu symptoms, headaches, heart racing, skin rash, sweating, tremor") were not symptoms of withdrawal.[20]

Heavy smokers are reported to burn 200 calories per day more than non-smokers eating the same diet.[124] Possible reasons for this phenomenon include nicotine's ability to increase energy metabolism or nicotine's effect on peripheral neurons.[123]

The 2008 Guideline suggests that sustained-release bupropion, nicotine gum, and nicotine lozenge be used "to delay weight gain after quitting."[6]:173–176 However, a 2012 Cochrane review concluded that "The data are not sufficient to make strong clinical recommendations for effective programmes" for preventing weight gain.[125]

Like other physically addictive drugs, nicotine withdrawal causes down-regulation of the production of dopamine and other stimulatory neurotransmitters as the brain attempts to compensate for artificial stimulation. Therefore, when people stop smoking, depressive symptoms such as suicidal tendencies or actual depression may result.[116][126] This side effect of smoking cessation may be particularly common in women, as depression is more common among women than among men.[127]

A recent study by The British Journal of Psychiatry has found that smokers who successfully quit feel less anxious afterwards with the effect being greater among those who had mood and anxiety disorders than those that smoked for pleasure.[128]

Within 5 years, the risk of stroke falls to the same as a non-smoker, and the risks of many cancers (mouth, throat, esophagus, bladder, cervix) decrease significantly

Within 10 years, the risk of dying from lung cancer is cut in half,[130] and the risks of larynx and pancreas cancers decrease

Within 15 years, the risk of coronary heart disease drops to the level of a non-smoker; lowered risk for developing COPD (chronic obstructive pulmonary disease)

The British doctors study showed that those who stopped smoking before they reached 30 years of age lived almost as long as those who never smoked.[131] Stopping in one's sixties can still add three years of healthy life.[131] A randomized trial from the U.S. and Canada showed that a smoking cessation program lasting 10 weeks decreased mortality from all causes over 14 years later.[132]

Another published study, "Smoking Cessation Reduces Postoperative Complications: A Systematic Review and Meta-analysis," examined six randomized trials and 15 observational studies to look at the effects of preoperative smoking cessation on postoperative complications. The findings were: 1) taken together, the studies demonstrated decreased likelihood of postoperative complications in patients who ceased smoking prior to surgery; 2) overall, each week of cessation prior to surgery increased the magnitude of the effect by 19%. A significant positive effect was noted in trials where smoking cessation occurred at least four weeks prior to surgery; 3) For the six randomized trials, they demonstrated on average a relative risk reduction of 41% for postoperative complications.[133]

In a 1997 U.S. analysis, the estimated cost per QALY varied by the type of cessation approach, ranging from group intensive counselling without nicotine replacement at $1108 per QALY to minimal counselling with nicotine gum at $4542 per QALY.[134]

The frequency of smoking cessation among smokers varies across countries. Smoking cessation increased in Spain between 1965 and 2000,[137] in Scotland between 1998 and 2007,[138] and in Italy after 2000.[139] In contrast, in the U.S. the cessation rate was "stable (or varied little)" between 1998 and 2008,[140] and in China smoking cessation rates declined between 1998 and 2003.[141]

Nevertheless, in a growing number of countries there are now more ex-smokers than smokers.[2] For example, in the U.S. as of 2010, there were 47 million ex-smokers and 46 million smokers.[142]